Blood vessels consist of two interacting cell types: endothelial cells, which form the inner lining of the vascular tube, and pericytes, which wrap around the vascular tube. While endothelial cells are the better characterized of the two, pericytes are now coming into focus as potentially important regulators of tumor angiogenesis. Pericytes constitute a heterogeneous population of cells, and their ontogeny and function, specifically in tumors, is not well understood. This project will test the hypothesis that tumor-associated PDGFRbeta+ perivascular cells are progenitor cells that have the capacity to differentiate into mature pericytes and that they are a critical vascular cell constituent for the maintenance and growth of tumor vessels. Specific Aim 1. Identify and characterize PDGFRbeta+ perivascular cells in normal and malignant tissues. We will characterize PDGFRbeta+ perivascular cells in three tumor types and in the respective normal tissues. Specific Aim 2. Study function of PDGFRbeta+ perivascular cells in tumor angiogenesis. We will examine the potential role of PDGFRbeta+ cells as pericyte progenitor cells and as survival mediators for endothelial cells. Specific Aim 3. Reveal the origin of PDGFRbeta+ perivascular cells in tumor angiogenesis. We will test whether tumor-associated PDGFRbeta+ perivascular cells originate from the bone marrow, or from adjacent normal tissue in which the tumor is embedded. The research addresses a novel aspect in tumor angiogenesis. It will test the hypothesis that the tumor-associated pericyte, the PDGFRbeta+ perivascular cell (PVC), is a functional and instrumental component of tumor vessels. The results will set an important foundation for therapeutic implications by exploiting PDGFRbeta+ PVC not only as novel targets for anti-angiogenic therapies in tumors but also as potentially important vascular cell constituents in tissues in which new and stable blood vessel formation is desired.